Dramatic increases in the incidence and severity of allergic asthma, eczema, hay fever and food allergy have been seen recently, particularly in children;every fourth child in the U.S. is affected. Manifestations of these allergic diseases are varied and progress over time. Given this chronological variation, the assessment of children at a single time point may not yield an accurate picture of allergic disease. We have a unique cohort of over 1,000 children characterized for asthma and allergy at birth (in 1989-1990) and ages 1, 2, 4, and 10 years. Using longitudinal data from this cohort we propose to identify time-dependent patterns of allergic disorders, which we term allergic trajectories. Genetic predisposition is a key factor underlying asthma and allergy, yet our knowledge of susceptibility genes for these inflammatory disorders is limited. To gain greater understanding of the mechanisms of allergic asthma and other allergies, we will investigate candidate genes thought to mediate allergic inflammation, IL4, IL4R, IL13, IL1 and IL1RN, in DNA samples collected from our cohort of children. We will use a novel approach to perform genetic association studies by using allergic trajectories as phenotypes instead of relying on parameters assessed at a single time point. In addition to genetic susceptibility, environmental exposures are thought to influence both the presence and severity of allergic diseases. However, the nature of the interaction between genes and the environment remains unclear. Thus, we will assess gene x environment interactions between selected candidate genes and common environmental exposures in cohort children. We have assembled a highly experienced multidisciplinary research team with expertise in genetics, epidemiology, clinical medicine (allergy and immunology) and biostatistics. With this team we will be able to build on a strong foundation of a thoroughly characterized childhood cohort study population by expanding the epidemiologic analyses of asthma and allergy, and beginning genetic association analyses of candidate genes. By determining genetic and environmental risk factors in this cohort, we will contribute information valuable to both health care professionals and parents regarding management practices to minimize risks to susceptible children.